Strategies for tumor imaging with radioiodinated phospholipid ether analogs.

The overall goal of my research was to explore various strategies for improving the targeting of meta-radioiodinated phospholipid ether analogs (PLE) to tumors. One strategy was to create structural analogs of the PLE's in order to elucidate the molecular requirements for tumor localization. It was discovered that placement of the radioiodine in the para position resulted in an increase in tumor uptake. Moreover, changes in the polar head group of 12-(p-iodophenyl)dodecylphosphocholine (NM-346) resulted in dramatic effects on the retention of these compounds in tumors. The choline polar headgroup was found to be critical for tumor uptake and retention. Secondly, efforts to improve targeting to liver tumors was explored by administration of radioiodinated PLE via the hepatic artery. For this study, VX2 tumor-bearing rabbits were utilized as the experimental model. Although this effort was unsuccessful, intravenous administration clearly delineated non-abdominal lesions such as breast tumors in two rodent tumor models. Finally, attempts were made to correlate tumor retention with cellular metabolism by various enzymes Tumor retention of PLE was not correlated with the actions of O-alkylglycerol monooxygenase or phospholipase C. However, some support for the role of phospholipase D was obtained. This work has significantly added to our understanding of the biodistribution and metabolic fate of radioiodinated PLE in tumor-bearing animals and to the molecular requirements for their tumor retention.PhDHealth and Environmental SciencesMedical imagingMedicinePharmacologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130409/2/9722134.pd